Therapeutic potential of PLK1 inhibition in triple-negative breast cancer

• Published in: Laboratory investigation Vol. 99; no. 9; pp. 1275 - 1286
• Main Authors: Ueda, Ai, Oikawa, Keiki, Fujita, Koji, Ishikawa, Akio, Sato, Eiichi, Ishikawa, Takashi, Kuroda, Masahiko, Kanekura, Kohsuke
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.09.2019; Nature Publishing Group US; Nature Publishing Group
• Subjects: 13/31; 13/51; 13/89; 13/95; 14/28; 631/67/1059/602; 692/699/67/1347; 96/2; 96/35; Apoptosis; Breast - metabolism; Breast cancer; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Deoxyribonucleic acid; DNA; Female; Gene Knockdown Techniques - methods; Humans; In vivo methods and tests; Inhibition; Inhibitors; Kinases; Laboratory Medicine; Mammary gland; Mammary glands; Medicine; Medicine & Public Health; Mitosis; Molecular Targeted Therapy; Pathology; Polo-like kinase; Polo-Like Kinase 1; Polyploidy; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; RNA, Small Interfering - genetics; siRNA; Therapeutic applications; Therapy; Triple Negative Breast Neoplasms - metabolism; Tumors
• ISSN: 0023-6837; 1530-0307; 1530-0307
• DOI: 10.1038/s41374-019-0247-4

Triple negative breast cancer (TNBC) is responsible for significant number of breast cancer-associated deaths because of lacking of successful molecular-targeted therapy. To explore a therapeutic target for TNBC, we performed a siRNA-mediated knockdown screening and identified Polo-like kinase 1 (PLK1) as a potential therapeutic target for TNBC. Knockdown of PLK1 as well as a small compound inhibitor for PLK1, BI-2536, induced G2/M arrest and created polyploid cell population, shown by increased DNA content and nuclear size. Inhibition of PLK1 eventually triggered apoptosis in multiple TNBC cell lines. In addition, we confirmed that PLK1 was significantly overexpressed in the tissues from TNBC patients compared with the tissues of normal mammary glands and benign breast tumors. Our data indicated that PLK1 plays a pivotal role in the regulation of mitosis of TNBC cells. Although future in vivo studies are warranted, targeting PLK1 by a selective inhibitor such as BI-2536 can be an attractive molecular-targeted therapy for TNBC.